title: Transcriptional responses of human aortic endothelial cells to nanoconstructs used in biomedical applications.
abstract: Understanding the potential toxicities of manufactured nanoconstructs used for drug delivery and biomedical applications may help improve their safety. We sought to determine if surface-modified silica nanoparticles and poly(amido amine) dendrimers elicit genotoxic responses on vascular endothelial cells. The nanoconstructs utilized in this study had a distinct geometry (spheres vs worms) and surface charge, which were used to evaluate the contributions of these parameters to any potential adverse effects of these materials. Time-dependent cytotoxicity was found for surfaced-functionalized but geometrically distinct silica materials, while amine-terminated dendrimers displayed time-independent cytotoxicity and carboxylated dendrimers were nontoxic in our assays. Transcriptomic evaluation of human aortic endothelial cell (HAEC) responses indicated time-dependent gene induction following silica exposure, consisting of cell cycle gene repression and pro-inflammatory gene induction. However, the dendrimers did not induce genomic toxicity, despite displaying general cytotoxicity.
authors.affiliation: Department of Pharmacology and Toxicology, Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah , Salt Lake City, Utah 84112, United States. philip.moos@utah.edu
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Moos
authors.forename: Matthew
authors.initials: M
authors.lastname: Honeggar
authors.forename: Alexander
authors.initials: A
authors.lastname: Malugin
authors.forename: Heather
authors.initials: H
authors.lastname: Herd
authors.forename: Giridhar
authors.initials: G
authors.lastname: Thiagarajan
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D050091:Dendrimers / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry / Q000494:pharmacology
chemical_list: D050091:Dendrimers; C531249:Poly(amidoamine); D011073:Polyamines; D012822:Silicon Dioxide